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Scientists Discover Protein That Fuels Alzheimer’s Disease, Promising New Treatments Expected

September 3, 2010

On behalf of its donors, the Alzheimer's Disease Research (ADR) program of the BrightFocus Foundation, is proud to have Dr. Greengard as an honorary board member and to have previously funded him for his work concerning phosphoproteins and Alzheimer's disease. Please read below about his important new discovery featured in Nature, the prominent medical journal.

Adapted from the Fisher Center for Alzheimer's Research Foundation

Fisher Center scientists have published a new finding that is being hailed as a potential paradigm shift in how researchers around the world will fight Alzheimer's disease. They have discovered a protein that is centrally involved in creating beta-amyloid. An over abundance of beta-amyloid kills brain cells and creates the devastating symptoms of Alzheimer's disease.

“Alzheimer's disease is a devastating disorder for which there are no satisfactory treatments. Our findings reveal that gamma-secretase activating protein is a potential target for a new class of anti-amyloid therapies,” says Dr. Greengard. The finding was published on September 1, 2010, in Nature online.

Researchers at the Fisher Center for Alzheimer's Disease Research laboratory, Drs. Gen He (lead author) and Paul Greengard have discovered a protein that stimulates the production of beta-amyloid, and therefore represents a major new advance in Alzheimer's disease research.

The protein, called gamma secretase activating protein (gSAP), is expected to become a major target for anti-amyloid drugs that inhibit the brain's ability to produce toxic beta-amyloid in Alzheimer's disease. Beta-amyloid is a substance found in the brain that becomes toxic in Alzheimer's disease and is responsible for most of the devastating symptoms of the disease. The researchers also discovered that gSAP is a target of the anti-cancer drug, Gleevec, which Fisher scientists previously showed could lower beta-amyloid levels in the brain. The new study showed that Gleevec lowers beta-amyloid production by binding to gSAP and preventing it from activating an enzyme called gamma secretase, which is responsible for producing beta-amyloid. In addition, the researchers showed that the inhibition of gSAP is not toxic to nerve cells, unlike many other experimental beta-amyloid inhibitor drugs that produce severe toxic reactions.

“We are working on selecting more potent compounds that selectively target gSAP and hopefully provide possible new treatments for Alzheimer's,” Dr. He says.

This new breakthrough from the laboratory of Nobel Prize winner Paul Greengard, however, suggests that treatments modeled on the blockbuster cancer drug Gleevec could be the solution. Hence, gSAP holds the promise of discovering highly specific anti-beta-amyloid drugs that will be safe to patients.

“Millions of people suffer from Alzheimer's disease, and treatment options are limited,” says Dr. Paul Greengard, Nobel Laureate and Director of the Fisher Center for Alzheimer's Disease Research laboratory at The Rockefeller University. “Existing drugs may mask symptoms for a time but do nothing to stop the relentless downward progression of Alzheimer's. What is needed are safe and effective medications that will halt the cause of the underlying disease. It is our hope that this gamma secretase activating protein will greatly add to the creation of safe and effective Alzheimer's treatments.”

Kent Karosen, President of the Fisher Center for Alzheimer's Research Foundation says, “We are so proud of the scientists we support, and would like to specifically congratulate Drs. He and Greengard for discovering this important protein. Their latest research is a potential paradigm shift in how scientists and doctors around the world will attack Alzheimer's.”

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Disclaimer: The information provided in this section is a public service of the BrightFocus Foundation, and should not in any way substitute for the advice of a qualified healthcare professional, and is not intended to constitute medical advice. Although we take efforts to keep the medical information on our website updated, we cannot guarantee that the information on our website reflects the most up-to-date research. Please consult your physician for personalized medical advice; all medications and supplements should only be taken under medical supervision. BrightFocus Foundation does not endorse any medical product or therapy.

Some of the content in this section is adapted from other sources, which are clearly identified within each individual item of information.

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